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Trial record 1 of 1 for:    NCT02580058
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A Study Of Avelumab Alone Or In Combination With Pegylated Liposomal Doxorubicin Versus Pegylated Liposomal Doxorubicin Alone In Patients With Platinum Resistant/Refractory Ovarian Cancer (JAVELIN Ovarian 200)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2017 by Pfizer
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT02580058
First received: October 16, 2015
Last updated: May 22, 2017
Last verified: May 2017
  Purpose
A Phase 3 global study comparing avelumab alone to avelumab plus PLD and to PLD alone to demonstrate that avelumab given alone or in combination with PLD is superior to PLD alone in prolonging Overall Survival in patients with platinum resistant/platinum refractory ovarian cancer.

Condition Intervention Phase
Ovarian Cancer
Biological: avelumab
Drug: PLD
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase 3, Multicenter, Randomized, Open-label Study Of Avelumab (msb0010718c) Alone Or In Combination With Pegylated Liposomal Doxorubicin Versus Pegylated Liposomal Doxorubicin Alone In Patients With Platinum-resistant/Refractory Ovarian Cancer

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: randomization up to approximately 20 months ]
    Overall survival was the duration from enrollment to death. For participants who are alive, overall survival was censored at the last contact.

  • Progression Free Survival (PFS) [ Time Frame: randomization up to approximately 20 months ]
    To demonstrate that avelumab given alone or in combination with PLD is superior to PLD alone in prolonging Progression Free Survival (PFS) in patients with platinum resistant/platinum refractory ovarian cancer.


Secondary Outcome Measures:
  • OR (Objective Response) [ Time Frame: Baseline up to approximately 20 months ]

    Number of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST. Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response.

    Per RECIST v1.0: CR defined as disappearance of all target lesions and non-target lesions. PR defined as ≥30% decrease in sum of the longest diameters dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST associated to non-progressive disease response for non target lesions.


  • PFS (Progression Free Survival) [ Time Frame: randomization up to approximately 20 months ]
    The period from study entry until disease progression, death or date of last contact.

  • DR (Duration of Response) [ Time Frame: first documentation of objective tumor response up to approximately 20 months ]
    Duration of response (DR) is defined, for patients with an objective response per RECIST v1.1, as the time from the first documentation of objective tumor response (CR or PR) to the first documentation of objective tumor progression or death due to any cause, whichever occurs first.

  • DC (Disease Control) [ Time Frame: Randomization up to approximately 20 months ]
    Defined as complete response (CR), partial response (PR), or stable disease (SD) 24 weeks according to the RECIST version 1.1 recorded from randomization until disease progression or death due to any cause. The DC rate (DCR) on each randomized treatment arm will be estimated by dividing the number of patients with CR, PR, or SD 24 weeks by the number of patients randomized to the treatment arm. The corresponding exact 2 sided 95% CI for the DC rates will be provided by treatment arm

  • Ctrough for avelumab [ Time Frame: pre dose and at the end of infusion (immediately before the end of avelumab infusion) on Days 1 and 15. ]
    Ctrough is defined as the trough plasma concentrate at the end of an avelumab interval

  • Cmax for avelumab [ Time Frame: pre dose and at the end of infusion (immediately before the end of avelumab infusion) on Days 1 and 15. ]
    Cmax defined as the maximum plasma concentration of avelumab

  • Cmax for PLD [ Time Frame: in the first 12 patients pre dose, immediately prior to end of infusion, and at 2, 6, 24, and 336 hours (Day 15) post start infusion of PLD on Day 1 of next dose. ]
    Cmax defined as the maximum plasma concentration of PLD

  • Vd (volume of distribution) for PLD [ Time Frame: in the first 12 patients pre dose, immediately prior to end of infusion, and at 2, 6, 24, and 336 hours (Day 15) post start infusion of PLD on Day 1 of next dose. ]
    Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug

  • CL (clearance) for PLD [ Time Frame: in the first 12 patients pre dose, immediately prior to end of infusion, and at 2, 6, 24, and 336 hours (Day 15) post start infusion of PLD on Day 1 of next dose. ]
    CL is a quantitative measure of the rate at which PLD is removed from the body

  • AUC (area under the concentration time curve) for PLD [ Time Frame: in the first 12 patients pre dose, immediately prior to end of infusion, and at 2, 6, 24, and 336 hours (Day 15) post start infusion of PLD on Day 1 of next dose. ]
    AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption

  • Incidence of Anti-Drug Antibody (ADA) [ Time Frame: prior to start of avelumab infusion on Day 1 and at end of treatment for up to 24 months. ]
    immunogenicity assessment for avelumab

  • EORTC QLQ C30 [ Time Frame: once a month before dosing, up to 24 months ]
    European Organization for Research and Treatment of Cancer Quality of Life Questionnaire: 30 question survey and includes 5 functional domain subscales, including a physical functioning sub scale, a role functioning subscale, an emotional functioning sub scale, a cognitive functioning sub scale and a social functioning subscale. Higher scores on the functioning domains are indicative of higher levels of functioning

  • EORTC QLQ OV28 [ Time Frame: once a month before dosing, up to 24 months ]
    European Organization for Research and Treatment of Cancer Quality of Life Questionnaire: 28 item instrument with seven (7) functional domain subscales. The 7 subscales include: (i) an abdominal/gastrointestinal symptom subscale (7 items); (ii) a peripheral neuropathy subscale (3 items); (iii) an other chemotherapy side effects subscale (7 items); (iv) a hormonal/menopausal symptoms subscale (2 items); (v) a body image subscale (2 items); (vi) an attitude to disease and treatment subscale (3 items) and (vii) a sexual function subscale (4 items)

  • FOSI [ Time Frame: once a month before dosing, up to 24 months ]
    a very brief ovarian cancer symptom index derived from the FACT O (ie, Functional Assessment of Cancer Therapy Ovarian) to measure symptom response to treatment for ovarian cancer. The 8 item FOSI includes items assessing worry about future deterioration, contentment with QoL, and lack of energy in addition to 5 questions to assess GI related symptoms

  • EuroQoL EQ 5D [ Time Frame: once a month before dosing, up to 24 months ]
    Euro Quality of Life: 6 item patient completed questionnaire designed to assess health status in terms of a single index value or utility score. There are 2 components to the EuroQol EQ 5D: a Health State Profile which has individuals rate their level of problems (no, some or moderate, extreme) in 5 areas (mobility, self care, usual activities, pain/discomfort, and anxiety/depression) and a Visual Analogue Scale (VAS) in which patients rate their overall health status from 0 (worst imaginable) to 100 (best imaginable). Published weights are available that allow for the creation of a single summary score. Overall scores range from 0 to 1, with low scores representing a higher level of dysfunction

  • Tumor Tissue Biomarkers [ Time Frame: Baseline, optional sample at disease progression ]
    May include but not limited to PD L1 expression and tumor infiltrating CD8+ T lymphocytes by IHC, and/or tissue expression of FoxP3, PD 1, PD L2

  • Nab (neutralizing antibodies) against avelumab [ Time Frame: performed if ADA is positive: prior to start of avelumab infusion on Day 1 and at end of treatment for up to 24 months. ]
    immunogenicity assessment for avelumab


Estimated Enrollment: 550
Actual Study Start Date: December 23, 2015
Estimated Study Completion Date: March 12, 2018
Estimated Primary Completion Date: March 12, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: avelumab
Arm A: avelumab alone
Biological: avelumab
10 mg/kg will be given as a 1 hour intravenous infusion (IV) every 2 weeks (Q2W) in 4 week cycles
Experimental: avelumab plus pegylated liposomal doxorubicin (PLD)
Arm B: avelumab plus PLD
Biological: avelumab
10 mg/kg will be given as a 1 hour intravenous infusion (IV) every 2 weeks (Q2W) in 4 week cycles
Drug: PLD
PLD (Arm B, Arm C) 40 mg/m2 will be given as a 1 hour IV infusion every 4 weeks (Q4W) in 4 week cycles
Other Name: doxorubicin, calyx
Active Comparator: PLD
Arm C: PLD alone
Drug: PLD
PLD (Arm B, Arm C) 40 mg/m2 will be given as a 1 hour IV infusion every 4 weeks (Q4W) in 4 week cycles
Other Name: doxorubicin, calyx

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed epithelial ovarian, fallopian tube, or peritoneal cancer, including malignant mixed Müllerian tumors with high grade serous component.
  • Platinum resistant/refractory disease, defined as disease progression within 180 days following the last administered dose of platinum therapy (resistant), or lack of response or disease progression while receiving the most recent platinum based therapy (refractory), respectively.
  • Received up to 3 lines of systemic anticancer therapy for platinum sensitive disease, most recently platinum containing, and no prior systemic therapy for platinum resistant disease
  • Measurable disease by investigator assessment with at least 1 unidimensional measurable lesion by RECIST v.1.1 that has not previously been irradiated
  • Active autoimmune disease that might deteriorate when receiving an immunostimulatory agents. Patients with diabetes type I, vitiligo, psoriasis, hypo or hyperthyroid disease not requiring immunosuppressive treatment are eligible.

Mandatory tumor biopsy must be performed prior to enrollment for all patients (unless there is a documented clinical contraindication). In addition, availability of archived FFPE tumor tissue should be confirmed. If a patient underwent tumor tissue collection within 3 months prior to enrollment with no intervening treatment, and the sample is provided, then a new de novo tumor biopsy is not required.

Exclusion Criteria:

  • Non epithelial tumor or ovarian tumors with low malignant potential (ie, borderline tumors).
  • Prior therapy with an anti PD 1, anti PD L1, anti PD L2, anti CD137, or anti cytotoxic T lymphocyte associated antigen 4 (CTLA 4) antibody (including ipilimumab, tremelimumab or any other antibody or drug specifically targeting T cell co stimulation or immune checkpoint pathways).
  • Known symptomatic brain metastases requiring steroids. Patients with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to study entry, have discontinued corticosteroid treatment for these metastases for at least 4 weeks prior to study entry and are neurologically stable.
  • Diagnosis of any other malignancy within 5 years prior to registration, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix.
  • Severe gastrointestinal conditions such as clinical or radiological evidence of bowel obstruction within 4 weeks prior to study entry, uncontrolled diarrhea in the last 4 weeks prior to enrollment, or history of inflammatory bowel disease.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02580058

Contacts
Contact: Pfizer CT.gov Call Center 1-800-718-1021

  Show 357 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02580058     History of Changes
Other Study ID Numbers: B9991009
2015-003091-77 ( EudraCT Number )
JAVELIN OVARIAN 200 ( Other Identifier: Alias Study Number )
Study First Received: October 16, 2015
Last Updated: May 22, 2017

Keywords provided by Pfizer:
platinum resistant
platinum refractory

Additional relevant MeSH terms:
Ovarian Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Doxorubicin
Liposomal doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 25, 2017